Frontiers in Computational Chemistry

Frontiers in Computational Chemistry presents contemporary research on molecular modeling techniques used in drug discovery and the drug development process: computer aided molecular design, drug discovery and development, lead generation, lead optimization, database management, computer and molecular graphics, and the development of new computational methods or efficient algorithms for the simulation of chemical phenomena including analyses of biological activity.
The Second volume of this series features nine different articles covering topics such as antibacterial drug discovery, high throughput screening, computational biochemistry with deMon2k, lipid bilayer analysis and much more.

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Computational Chemistry for Photosensitizer Design and Investigation of DNA Damage

Pp. 27-70 (44)

Kazutaka Hirakawa

Abstract

Computational chemistry can be used for the prediction of photochemical
reactivity and the design of photosensitizers for cancer phototherapy. For example, the
activity of a photosensitizer for DNA damage can be estimated from the calculation of the
HOMO energy of the molecules. In general, DNA damage is mediated by the following
two processes: 1) photo-induced electron transfer from the DNA base to the photoexcited
photosensitizer and 2) base modification by singlet oxygen generation through photoenergy
transfer from the photosensitizer to oxygen. The DNA-damaging activity of the
photosensitizer through electron transfer is closely related to the HOMO energy level of the
molecule. It has been demonstrated that the extent of DNA damage photosensitized by
xanthone analogues is proportional to the energy gap between the HOMO level of the
photosensitizer and that of guanine. In addition, computational chemistry can be used to
investigate the mechanism of the chemopreventive effect on phototoxicity. Furthermore,
the molecular orbital calculation is useful to design a photosensitizer in which the activity
of singlet oxygen generation is controlled by DNA recognition. Singlet oxygen is an
important reactive oxygen species to attack cancer. The control of singlet oxygen
generation by DNA is necessary to achieve the tailor-made cancer photo-therapy. Several
porphyrin photosensitizers have been designed on the basis of the molecular orbital
calculation to control the activity of singlet oxygen generation.